New mouse model will help study olfactory loss in sinusitis

Published: Wednesday, July 23, 2008, 15:11 [IST]

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Washington, July 23 : Scientists at a Johns Hopkins laboratory have genetically engineered mice to produce live models that may enable them to better understand olfactory loss often seen among sinusitis patients.

The researchers say that their mouse models do not have one key sense that is essential to tasting food or sensing danger from foul odours.

They, however, add that this olfactory loss among the mice is reversible.

"A sense of smell in good working order is essential to our quality of life, and these genetically engineered mice give us the first real animal model for better understanding, treating and preventing people from suffering a loss of olfactory function due to sinonasal inflammation," says sinusitis expert Dr. Andrew Lane, who led the team that developed the olfactory-compromised mice.

"And because we can turn on and off the inflammation in these mice, we really can mimic how the most overlooked and very disabling aspect of sinusitis, the loss of smell, or anosmia, plays out in people," adds Lane, an associate professor at the Johns Hopkins University School of Medicine.

On the significance of having live mouse models, Lane says: "Until now, the lack of realistic animal models for each of the key symptoms of chronic inflammation in the nasal tissue - such as the growth of nasal polyps, the loss of the sense of smell, swollen sinus tissue, or clogged and runny noses - has slowed sinusitis research and hindered our search for therapies."

He says that another key advantage to the new sinusitis mouse is that it can be more easily studied than human olfactory tissue that is surgically difficult to cut out from deep inside the skull, and sits dangerously close to the brain.

To ensure that their the model worked, the researchers induced sinusitis among the mice by mixing a drug in their water for nearly two months, and tested samples of olfactory tissue weekly for any sense of smell in response to various odours.

They found that the sense of smell, as gauged by minute electrical currents in olfactory tissue, dropped progressively, by 50 percent within two weeks, and stopped completely after six weeks.

Viewing the issue under microscope, the researchers observed that white blood cells were visible, a telltale sign of inflammation. Olfactory nerve cells had nearly disappeared.

However, when the researchers stopped the drug-induced sinusitis, olfactory nerve cells rebounded and grew back within a couple of weeks, "proving that what we have is a mouse with reversible olfactory loss due to inflammation, which should speed up our learning more about the disease and testing new therapies," says Lane.

"Ultimately, we hope to develop treatments that allow the sense of smell to recover, even in the presence of a hostile inflammatory environment due to sinusitis," Lane adds.

He says that in another phase of the research, other anti-inflammatory drugs like infliximab (Remicade), which is used to treat arthritis, will be tested to see whether they can spur growth of olfactory neurons during sinusitis.

Lane also plans to add more sinusitis features to the animal model, including progressive swelling of sinus tissue and rhinitis.